Abstract 3552: Personalized neoantigen cancer vaccine assembled on DC targeting antibody improves cancer immunity
Authors: Yuji Mishima, Fumiko Isoda, Noriko Matsumoto, Noriko Watanabe, Kazushi Hiranuka, Takashi Yamada, Norihiro Fujinami, Manami Shimomura, Toshihiro Suzuki, Tetsuya Nakatsura, Norihiro Nakamura
Journal: Cancer Research (2022)

Abstract Background: Personalized neoantigen cancer vaccines have recently showed marked therapeutic potential in both preclinical and early phase clinical studies. However, significant challenges remain in the accurate prediction of neoepitopes and the efficient delivery of the vaccine components for eliciting potent antitumor T cell responses. To overcome these challenges, we have developed novel vaccine platform designated BP1209, which is characterized by being composed of neoantigen peptides that contain a high affinity binding motif for human antibodies. Methods: We developed vaccine with enhanced efficacy designed to form a complex with checkpoint antibodies. The vaccine instantly assembles a divalent peptide-antibody complex by simply mixing with therapeutic antibodies in physiological condition. We evaluated the efficacy of BP1209 vaccine in combination with DC-targeting antibodies in vivo. Next, we generated a series of neoantigen peptides in both murine and human origins using in-house bioinformatic algorithms and evaluated the advantages of BP1209 vaccine. Results: BP1209 vaccine showed robust T-cell response and anti-tumor activity when combined with anti-CD40 agonistic antibody or atezolizumab compared with a control peptide vaccine or the antibody alone. Treatment of BP1209 murine neoantigen vaccine to syngeneic tumor bearing mice exhibited robust anti-tumor response resulting in complete tumor regression in therapeutic setting. Preclinical evaluation of neoantigen vaccines from murine and human tumors showed notably increased CD8+ T cell response even for epitopes that do not respond with a conventional long peptide vaccine. Further analysis of DCs and T cells induced by BP1209 suggested that peptide delivery was mediated by increased cross-presentation of epitope peptides on DCs supported by DC maturation by the checkpoint antibody and increased vaccine peptide uptake by the antibody mediating peptide delivery. TCR repertoire analysis of the tumor infiltrating lymphocytes (TILs) of vaccinated mice revealed remarkable accumulation of clonal CTLs in the BP1209 vaccinated group. Conclusions: BP1209 cancer vaccine dramatically improves T-cell response and anti-tumor activity over conventional long-peptide vaccines. We demonstrated that the enhancement of vaccine potency was achieved not only by the function of the antibodies on DCs but mainly by the increased antigen delivery to DCs. Enhanced T-cell response was more remarkable in CD8+ T cells, especially in clonal expansion of the CTL in TILs, suggesting that BP1209 vaccine facilitates antigen cross-presentation and inducing functional CTLs. Analysis using a number of predicted neoantigen peptides showed that the BP1209 vaccine enhances the vaccine efficacy independent of epitope sequences. Thus, our new platform of cancer vaccines provides a critical solution to enhance personalized neoantigen vaccines. Citation Format: Yuji Mishima, Fumiko Isoda, Noriko Matsumoto, Noriko Watanabe, Kazushi Hiranuka, Takashi Yamada, Norihiro Fujinami, Manami Shimomura, Toshihiro Suzuki, Tetsuya Nakatsura, Norihiro Nakamura. Personalized neoantigen cancer vaccine assembled on DC targeting antibody improves cancer immunity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3552.